After obtaining graduate and postdoctoral training in basic Cell Biology, I recently changed the focus of my research to study pathogens transmitted by arthropods. To pursue this new direction of study, I returned to Yale and joined the section of Rheumatology as a postdoctoral fellow to work on Lyme disease. I also enrolled as a part- time student (MPH) at the Yale School of Public Health which as a strong training program in vector-borne diseases. In July 1997 I will be joining the faculty of the section of Rheumatology to continue my research on Lyme disease. Since Lyme disease is a new area of research for me, I would greatly benefit from an additional period of mentored research at Yale during my initial years on the faculty. My research proposal aims to test the hypothesis that Borrelia burgdorferi, the most common cause of infectious arthritis in the USA, relies on differential gene expression in order to leave the tick vector and successfully infect the vertebrate host. The principal goals of this proposal are to characterize B. burgdorferi genes selectively expressed in the vector and to develop a strategy for blocking transmission and preventing Lyme arthritis. Specifically, studies will be initiated to 1) identify B. burgdorferi genes selectively expressed in ticks, 2) characterize the spatial and temporal pattern of expression of these genes within the vector, 3) to test B. burgdorferi genes expressed in the vector as vaccines for blocking transmission from the vector to the host. Concurrently with experiments to characterize novel genes, studies will be initiated with B. burgdorferi outer surface protein (Osp) A. OspA is primarily expressed in the vector and an OspA based Lyme disease vaccine currently in clinical trials protects hosts by killing spirochetes within feeding ticks and blocking transmission. Detailed experiments will be done using the OspA vaccine as a model to understand how antibodies block transmission from the vector to the host. This study will provide insight into tick-borne transmission of bacterial pathogens and lead to novel strategies for blocking transmission and preventing Lyme arthritis.